Controlled Cyclic Stretching of Tissue Engineered Heart Valves: Effects on Mechanical Properties and ECM Organization

Tissue engineering provides a means to create fully functional tissue-equivalents that can grow, repair and remodel in vivo. Our laboratory’s approach to fabricating artery- and heart valve-equivalents utilizes cell-seeded fibrin gels. However, even after 4–5 weeks of static incubation, the mechanical properties of these constructs are below those of native tissue. Previous studies in our laboratory have shown a significant role of mechanical stretching in improving properties of collagen-based tissue constructs (Isenberg and Tranquillo, 2003). We examined the effects of cyclic distention (CD) of cell-seeded fibrin-based tubular constructs (TC) and valve-equivalents (VE) after five weeks of culture. We used human dermal fibroblasts and porcine valve interstitial cells as the cell sources. Circumferential strain amplitudes from 2.5% to 15% were applied to evaluate the effects of CD on remodeling of the TC. We further hypothesized that during long-term conditioning, cells adapt to CD of constant strain amplitude, diminishing the remodeling into tissue. We tested this hypothesis by applying step-wise incremental CD (ICD) from 5%–15% strain amplitude and compared this group to a set of samples subject to CD of constant strain amplitude in this range. Based on the outcome of the cyclic distension study with tubular constructs, we applied CD to VE in a novel bioreactor.